Pyridine compounds as subtype selective modulators of alpha2b and /or alpha 2c adrenergic receptors

Abstract

The invention relates specifically to the use of certain 4-[1-(1H-Imidazol-4-yl)-ethyl]-2,3-substituted pyridine compounds and pharmaceutical compositions thereof to treat disorders associated with selective subtype alpha 2 adrenergic receptor modulation.

1 . A compound having the structure: 
       
         
           
           
               
               
           
         
         Wherein: 
         R 1  and R 2  independently=H, CH 2 OR 3 , CH 2 SR 3 , CH 2 N(R 4 )(R 5 ), C 1 -C 4  alkyl, halogens, CF 3 , CN, C 2 -C 4  alkenyl, C 2 -C 4  alkynyl 
         R 3 =H, C 1 -C 4  alkyl 
         R 4  and R 5  independently=H, alkyl 
         R 1  and R 2  may be fused to form a saturated ring
   —CH 2 —X—(CH 2 ) n —CH 2 —
 
 
         X=O, S, CH 2 , NR 3    
         n=0, 1, 2 
         and both enantiomers (R and S) and pro-drugs at the hydroxyl, amino, or thiol site or any combination thereof or pharmaceutically acceptable salts, hydrates, solvates, crystal forms, proisomers, pro-drugs, tautomers, enantiomers and diastereomers. 
       
     
     
         2 . The compound of  claim 1  wherein R 1  is CH 2 OR 3  and R 2  is H. 
     
     
         3 . The compound of  claim 2  wherein R 3  is H. 
     
     
         4 . The compound of  claim 1  wherein R 1  CH 2 OR 3  and R 2  is CH 3 . 
     
     
         5 . The compound of  claim 1  wherein R 1  is H and R 2  is CH 2 OH. 
     
     
         6 . The compound of  claim 1  wherein R 1  is CH 3  and R 2  is CH 2 OH. 
     
     
         7 . A compound according to  claim 1  selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         8 . A method of activating an alpha 2B or alpha 2C receptor in a mammal by administering a compound according to  claim 1  to the alpha 2B or alpha 2C receptor. 
     
     
         9 . A method of treating pain in a mammal by administering a compound according to  claim 1 . 
     
     
         10 . The method of treating pain according to  claim 9 , wherein the compound binds to the alpha 2B or alpha 2C receptor. 
     
     
         11 . The method of  claim 9  wherein the pain is chronic pain. 
     
     
         12 . The method of  claim 11  wherein the chronic pain is neuropathic pain. 
     
     
         13 . The method of  claim 11  wherein the chronic pain is associated with fibromyalgia. 
     
     
         14 . The method of  claim 9  wherein the pain is visceral pain.